ORGANIC LETTERS
Efficient Entry into Medium-Ring Keto-Lactones. The Ruthenium Tetraoxide-Promoted Oxidative Cleavage of β-Hydroxyethers
2003 Vol. 5, No. 8 1337-1339
Helena M. C. Ferraz* and Luiz S. Longo, Jr. Instituto de Quı´mica, UniVersidade de Sa˜ o Paulo, CEP 05508-900, Sa˜ o Paulo SP, Brazil
[email protected] Received February 19, 2003
ABSTRACT
A new use of ruthenium tetraoxide is reported. The catalytic oxidative cleavage of hexahydro-benzofuran-3a-ols led to nine-membered ring keto-lactones in moderate to good yields and high purity. The reaction is clean and easily performed using catalytic amounts of ruthenium trichloride and an excess of sodium periodate as a cooxidant.
The synthesis of medium-ring compounds (those containing from 8 to 11 atoms) remains a challenge for organic chemists. Several efforts have been made toward the development of efficient methods for the preparation of these systems,1 since they are encountered in many biologically important natural products such as the medium-ring ethers (+)-obtusenyne,2 (+)-laurallene,3 and (-)-isolaurallene,4 besides the wellknown brevetoxins5 and taxol.6 Medium-ring lactones are also found in nature. Examples are the octalactins A and B,7 the nine-membered ring halicholactone and neo-
halicholactone,8 and the cephalosporolides B and C.9 Some of them are outlined in Figure 1. Cyclization strategies toward medium-ring lactones are often inhibited due to entropic factors and transannular interactions. For instance, the rate of lactonization of ω-bromo alkanoic acid to the corresponding nine-membered ring lactone is almost zero.10 Many other methodologies for preparing medium-ring lactones have been reported11 such as the ionic12 and radical13 cleavage of saturated bicyclic hemiketals, the oxidative
(1) For reviews, see: (a) Yet, L. Chem. ReV. 2000, 100, 2963. (b) Nubbemeyer, U. Eur. J. Org. Chem. 2001, 1801. (2) (a) Fujiwara, K.; Awakura, D.; Tsunashima, M.; Nakamura, A.; Honma, T.; Murai, A. J. Org. Chem. 1999, 64, 2616. (b) Howard, B. M.; Schulte, G. R.; Fenical, W.; Solheim, B.; Clardy, J. Tetrahedron 1980, 36, 1747. (c) King, T. J.; Imre, S.; O ¨ ztuna, A.; Thomson, R. H. Tetrahedron Lett. 1979, 1453. (3) (a) Crimmins, M. T.; Tabet, E. A. J. Am. Chem. Soc. 2000, 122, 5473. (b) Fukuzawa, A.; Kurosawa, E. Tetrahedron Lett. 1979, 2797. (4) (a) Crimmins, M. T.; Emmitte, K. A. J. Am. Chem. Soc. 2001, 123, 1533. (b) Crimmins, M. T.; Emmite, K. A.; Choy, A. L. Tetrahedron 2002, 58, 1817. (c) Kurata, K.; Furusaki, A.; Sueturo, K.; Katayama, C.; Suzuki, T. Chem. Lett. 1982, 1031. (5) (a) Nicolaou, K. C.; Rutjes, F. P. J. T.; Theodorakis, E. A.; Tiebes, J.; Sato, M.; Untersteller, E. J. Am. Chem. Soc. 1995, 117, 1173. (b) Nicolaou, K. C.; Yang, Z.; Shi, G. Q.; Gunzner, J. L.; Agrios, K. A.; Gatner, P. Nature 1998, 392, 264. (6) Nicolaou, K. C.; Guy, R. K. Angew. Chem., Int. Ed. Engl. 1995, 34, 2079.
(7) (a) Tapiolas, D. M.; Roman, M.; Fenical, W.; Stout, T. J.; Cardy, J. J. Am. Chem. Soc. 1991, 113, 4682. (b) Buszek, K. R.; Sato, N.; Jeong, Y. Tetrahedron Lett. 2002, 43, 181. (8) (a) Niwa, H.; Wakamatsu, K.; Yamada, K. Tetrahedron Lett. 1989, 30, 4543. (b) Critcher, D. J.; Connolly, S.; Wills, M. J. Org. Chem. 1997, 62, 6638. (c) Takemoto, Y.; Baba, Y.; Saha, G.; Nakao, S.; Iwata, C.; Tanaka, T.; Ibuka, T. Tetrahedron Lett. 2000, 41, 3653. (9) Ackland, M. J.; Hanson, J. R.; Hitchcock, P. B.; Ratcliffe, A. H. J. Chem. Soc., Perkin Trans. 1 1985, 843. (10) Illuminati, G.; Mandolini, L. Acc. Chem. Res. 1981, 14, 95. (11) For a review concerning medium-ring lactones, see: Rousseau, G. Tetrahedron 1995, 51, 2777. (12) (a) Posner, G. H.; Webb, K. S.; Asirvatham, E.; Jew, S.-S.; Degl’Innocenti, A. J. Am. Chem. Soc. 1988, 110, 4754. (b) Mahajan, J. R.; DaSilva, C. R. J. Braz. Chem. Soc. 1990, 1, 87. (13) (a) Suginome, H.; Yamada, S. Tetrahedron 1987, 43, 3371. (b) Arencibia, M. T.; Freire, R.; Perales, A.; Rodriguez, M. S.; Sua´rez, E. J. Chem. Soc., Perkin Trans. 1 1991, 3349.
10.1021/ol0342958 CCC: $25.00 Published on Web 03/28/2003
© 2003 American Chemical Society
Table 1. RuO4-Promoted Oxidative Cleavage of 1b-da
Figure 1. Natural medium-ring lactones.
cleavage of unsaturated bicyclic compounds promoted by ozone, PCC, or mCPBA,14 and the cleavage of bicyclic 1,2diols.15 In 1985, Torii and co-workers reported a single example of the oxidative cleavage of an enol ether by ruthenium tetraoxide, which led to a ten-membered ring ketolactone.16 Recently, we reported the preparation of a series of hexahydro-benzofuran-3a-ols (1a-d) by thallium trinitratepromoted cyclization of homoallylic alcohols.17 One of the possible synthetic applications of these ethers could be the construction of R,β-unsaturated lactones, an important class of natural products. For example, the cyclic ether 1a could be transformed into isomintlactone,18 through dehydration followed by allylic oxidation.19 Nevertheless, the hydroxyl group of 1a proved to be very resistant to several dehydration conditions. We decided then to run a prior oxidation of 1a to the corresponding lactone 2, which would easily undergo the desired dehydration. Thus, the cyclic ether 1a was submitted to treatment with RuO4 generated in situ from catalytic amounts of ruthenium trichloride (RuCl3‚nH2O) and an excess of sodium periodate in a biphasic solvent system (H2O/CCl4/CH3CN ) 3:2:2).20 Somewhat surprisingly,21 the isolated product was the nine-membered ring keto-lactone 3a, obtained in very good yield (Scheme 1).
a Reagents and conditions: 2.4 mol % RuCl .nH O, 4.1 equiv of NaIO , 3 2 4 H2O/CCl4/CH3CN (3:2:2), rt, 75 min.
It is noteworthy that the keto-lactones 3a-d were obtained with a high degree of purity. No further purification was necessary, since neither significant impurities nor byproducts were detected in the 1H and 13C NMR spectra of the crude products.22 Moreover, the simple filtration of the concentrated organic extracts on a small silica gel pad was sufficiently efficient to hold the ruthenium dioxide formed during the course of the reactions. It has been postulated that the order of reactivity of C-H bonds toward the RuO4-promoted oxidation of ethers is CH2 > CH.23 However, we observed an inversion of regiochemistry in the reaction of the cyclic ethers 1a-d with RuO4, since carbon 7a (CH) was oxidized in preference to carbon 2 (CH2), as exemplified for 1a in Scheme 2.
Scheme 2
Scheme 1 a
Additional evidence of this inversion of regiochemistry was observed in the RuO4-promoted oxidation of the
a Reagents and conditions: 2.4 mol % RuCl ‚nH O, 4.1 equiv 3 2 of NaIO4, H2O/CCl4/CH3CN (3:2:2), rt, 75 min (81%).
This result prompted us to submit the cyclic ethers 1b-d to the same treatment. Thus, the keto-lactones 3b-d were obtained in moderate to good yields, as shown in Table 1. 1338
(14) (a) Mahajan, J. R.; Arau´jo, H. C. Synthesis 1975, 54. (b) Mahajan, J. R.; Arau´jo, H. C. Synthesis 1976, 111. (15) Bond, S.; Perlmutter, P. Tetrahedron 2002, 58, 1779. (16) Torii, S.; Inokuchi, T.; Kondo, K. J. Org. Chem. 1985, 50, 4980. (17) Ferraz, H. M. C.; Longo, L. S., Jr.; Zukerman-Schpector, J. J. Org. Chem. 2002, 67, 3518. (18) Takahashi, K.; Someya, T.; Muraki, S.; Yoshida, T. Agric. Biol. Chem. 1980, 44, 1535. (19) For a similar sequence leading to mintlactone, see: Ferraz, H. M. C.; Grazini, M. V. A.; Ribeiro, C. M. R.; Brocksom, U.; Brocksom, T. J. J. Org. Chem. 2000, 65, 2606. (20) These conditions were first reported by Sharpless and co-workers in 1981 and were used to oxidize several functional groups. Carlsen, H. J.; Katsuki, T.; Martin, V. S.; Sharpless, K. B. J. Org. Chem. 1981, 46, 3936. Org. Lett., Vol. 5, No. 8, 2003
hexahydro-benzofuran-3-ols 4a and 4b,24 which bear the hydroxyl group in another position. These ethers afforded, as the major product, the 2-acetyl-5-methyl-cyclohexanone (5), which is probably formed by the oxidation of the tertiary carbon 7a (Scheme 3).
Scheme 3
Scheme 4
a
Although the reaction mechanism remains unclear, the presence of the hydroxyl group in the cyclic ethers seems to play an important role in the chemoselectivity displayed by RuO4.26 It is of note that similar bicyclic ethers, without the hydroxyl group, afforded exclusively the corresponding products of oxidation of the secondary carbon.27 The results described herein represent a novel and efficient procedure for the synthesis of medium-sized lactones. At the moment, the application of this methodology to the synthesis of lactones of different sizes is in progress in our laboratory. a Reagents and conditions: 5.0 mol % RuCl ‚nH O, 4.1 equiv 3 2 of NaIO4, H2O/CCl4/CH3CN (3:2:2), rt, 30 min for 4a and 4 h for 4b (48% for 4a and 40% for 4b).
The fact that the equatorial tertiary C-H bonds of 1a-d and 4a were oxidized faster than the axial tertiary C-H bond of 4b agrees with the literature information about steric requirements for the oxidation reaction.25 Moreover, the less reactive cyclic ether 4b afforded minor amounts of the oxidation products of secondary carbon 2. The products 6 and 7 were obtained in 12 and 15% yields, respectively.
Acknowledgment. The authors wish to thank FAPESP, CNPq, and CAPES for financial support. We also thank Prof. Ronaldo A. Pilli from the University of Campinas for his help in carrying out the HRMS and Tiago O. Vieira and Prof. Luiz F. Silva Jr. for fruitful suggestions. Supporting Information Available: Experimental procedures for the RuO4-promoted oxidative cleavage of β-hydroxyethers 1a-d and 4a-b and structural data and NMR spectra of keto-lactones 3a-d. This material is available free of charge via the Internet at http://pubs.acs.org. OL0342958
In a preliminary experiment, the oxidative cleavage of the β-hydroxyether 8 led to the ten-membered ring keto-lactone 9, in a nonoptimized yield of 50% (Scheme 4). (21) For examples of the chemoselectivity displayed by RuO4 in the oxidation of tetrahydrofuran and tetrahydropyran derivatives, see: Smith, A. B., III; Scarborough, R. M., Jr. Synth. Commun. 1980, 10, 205.
Org. Lett., Vol. 5, No. 8, 2003
(22) For 1H and 13C NMR spectra of keto-lactones 3a-d, see Supporting Information. (23) Bakke, J. M.; Frohaug, A. E. J. Phys. Org. Chem. 1996, 9, 310. (24) Hexahydro-benzofuran-3-ols 4a and 4b were prepared by a previously reported procedure. Ferraz, H. M. C.; Ribeiro, C. M. R.; Grazini, M. V. A.; Brocksom, T. J.; Brocksom, U. Tetrahedron Lett. 1994, 35, 1497. (25) Reactivity of C-H bonds in cyclohexane systems toward RuO4promoted oxidations of hydrocarbons: axial secondary C-H, relative rate ) 1; equatorial secondary C-H, relative rate ) 9; axial tertiary C-H, relative rate ) 47; and equatorial tertiary C-H, relative rate ) 444. Bakke, J. M.; Bethell, D. Acta Chem. Scand. 1992, 46, 644. (26) ) Only substrate 4b underwent oxidation of both tertiary and secondary C-H bonds. (27) ) Kitagawa, I.; Tsujii, S.; Nishikawa, F.; Shibuya, H. Chem. Pharm. Bull. 1983, 31, 2639.
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